Pre-pregnancy and gestational interventions to prevent childhood obesity.

Childhood obesity is a significant global health issue with complex and multifactorial origins, often beginning before conception and influenced by both maternal and paternal health. The increased prevalence of pre-pregnancy obesity and gestational diabetes mellitus in women of reproductive age contributes to a heightened risk of metabolic dysfunction in offspring. Current clinical practices often implement lifestyle interventions after the first trimester, and have limited success, implying that they miss a critical window for effective metabolic adjustments. This review examines the limitations of lifestyle interventions during pregnancy in improving perinatal outcomes and highlights the importance of initiating such interventions before conception to positively impact parental health and fetal development. A re-evaluation of strategies is needed to enhance the metabolic health of prospective parents as a preventive measure against childhood obesity.

Gestational diabetes: an update sixty years after O'Sullivan and Mahan.

Sixty years after the landmark publication by O'Sullivan and Mahan, the current paper seeks to review and place into context the importance of gestational diabetes (GDM) both as a marker of increased risk of adverse maternal and fetal pregnancy outcomes and as an indicator of future maternal and infant health risks. We review the evolution of GDM as a diagnosis, the ongoing debate regarding diagnostic approaches, the underlying pathophysiology, the epidemiology and the importance of GDM in the context of the global epidemics of diabetes and obesity. Focusing on clinical management, we review lifestyle based therapy and pharmacotherapy for GDM, consider obstetric management and outline the short term and lifelong health risks posed by a GDM diagnosis.

The association of fetal growth rate and growth in first year of life with childhood overweight: a cohort study.

BACKGROUND: There is an increasing focus on the first 1000 days from conception to two years of age as a period of importance for future weight. We aimed to describe the interaction between fetal and infant growth and their association with and ability to predict childhood overweight. METHODS: We used routinely collected fetal growth data from Aarhus University Hospital and child growth data from Aarhus Municipality, 2008-2018. The outcome was overweight at age 5-9 years. The fetal growth rates at weeks 28 and 34 were extracted from individual trajectories using mixed models. We identified patterns of infant BMI Z-score growth using latent class analysis and estimated odds ratios of overweight at age 5-9 years dependent on fetal and infant growth. Predictive capabilities were assessed by comparing areas under the ROC-curves (AUCROC) of the prediction models. RESULTS: In 6206 children, we identified three infancy growth patterns: average, accelerated, and decelerated growth. We found 1.09 (95% CI: 1.06-1.12) greater odds of being overweight for every 10 g/week increase in fetal growth rate at week 34. Compared with average growth, accelerated infant growth was associated with 1.52 (95% CI: 1.20-1.90) greater odds of overweight. Combining fetal and infant growth, children with average fetal growth and accelerated infant growth had 1.96 (95% CI: 1.41-2.73) greater odds of overweight. Fast fetal growth with decelerated infant growth was not associated with being overweight (OR: 0.79 (95% CI: 0.63-0.98)), showing that infant growth modified the association between fetal growth and overweight. When fetal growth was added to a prediction model containing known risk factors, the AUCROC remained unchanged but infant growth improved the predictive capability (AUCROC difference: 0.04 (95% CI: 0.03-0.06)). CONCLUSION: Fetal and infant growth were independently associated with overweight, but distinct combinations of fetal and infant growth showed marked differences in risk. Infant, but not fetal, growth improved a prediction model containing known confounders.

Maternal glucose homeostasis during pregnancy in women with overweight or obesity and offspring metabolic health.

Gestational diabetes mellitus (GDM) adversely affects offspring glucose homeostasis and risk of developing obesity. Here, we examined the association between glycemia in pregnant women with overweight or obesity without GDM and offspring metabolic health. Maternal fasting glucose concentrations and glucose 2-h after an oral glucose tolerance test (OGTT) were measured in 208 women with a pre-pregnancy body mass index (BMI) of 28-45 kg/m2 without GDM. Offspring outcomes were collected at birth, 3, and 5 years of age. Linear mixed models with time as fixed factor and subject ID as random effects were used for analysis. No associations were found between maternal fasting or 2-h glucose concentrations with offspring glucose and insulin concentrations from birth to 5 years of age. However, maternal fasting glucose in GW 28 and 36, and 2-h OGTT glucose in GW 28 were positively associated with C-peptide concentration at birth. Maternal fasting glucose concentrations in GW 28 and 36 were positively associated with weight-for-length, and maternal fasting glucose in GW 36 was associated with BMI z-score at birth. In summary, blood glucose in pregnant women with overweight or obesity is positively associated with offspring C-peptide concentration, weight-for-length, and BMI z-score at birth, even in the absence of GDM.

Diabetes in pregnancy and offspring cardiac function: a systematic review and meta-analysis.

Introduction: Diabetes in pregnancy is associated with impaired offspring cardiac function. The objective of this systematic review was to determine the effect of diabetes in pregnancy on cardiac function in the offspring measured by echocardiography. Methods: PubMed, Embase, Cochrane CENTRAL and Web of Science databases were searched from 1992 to June 27, 2023. Studies reporting offspring (age < 18 years) cardiac function by echocardiography compared between any type of diabetes in pregnancy and healthy control pregnancies were included. Study selection, quality assessment and risk of bias was independently performed by two reviewers. Meta-analyses was performed where possible. Results: Thirty-one observational studies were included 1,679 cases and 2,694 controls. In the first week of life (23 studies, n = 2,663), intraventricular septum diastolic diameter (hypertrophy) was increased, while myocardial performance index (global function) and LV E/A-ratio (diastolic function) were decreased. No difference was found for left ventricular ejection fraction (systolic function). At 1-6 months (4 studies, n = 454) studies found hypertrophy, and decreased global function, but no difference in systolic or diastolic function. At 1-8 years (7 studies, n = 1,609) no difference was found. The available data did not allow for sub-analysis based on the type of diabetes, treatment, or glycemic control. Conclusions: Diabetes in pregnancy is associated with cardiac hypertrophy and impaired global cardiac function in infants up to six months old. The few studies reporting on older children found no difference in the parameters investigated. Longitudinal studies employing more advanced echocardiographic measures or MRI are needed to evaluate consequences for long-term cardiac health. Systematic Review Registration: https://www.crd.york.ac.uk/, identifier (CRD42022312471).

The effect of twin pregnancy in intrahepatic cholestasis of pregnancy: A case control study.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is one of the most common hepatic disorders during pregnancy, and the etiology is thought to be multifactorial including both environmental and hormonal contributions. In twin pregnancies, the fetal and placental mass is generally greater than in singleton pregnancies, and is, theoretically, likely to have a greater influence upon the maternal hepatic metabolism compared to singleton pregnancy. The aim of this study was to compare ICP in twin and singleton pregnancies according to ICP characteristics, time of diagnosis, serum bile acid levels, pharmacological treatment, and pregnancy outcomes. MATERIAL AND METHODS: This case control study was undertaken at Aarhus University Hospital, Denmark, from 2012 to 2019. The study comprised 51 women with twin pregnancies and ICP. These women were matched with 153 women with twin pregnancies without ICP and 153 women with singleton pregnancies with ICP, respectively. Three controls were matched per case, and data obtained from medical records and Danish obstetrical databases were compared. RESULTS: We found a significantly lower gestational age at ICP diagnosis in twin pregnancies (227 vs. 242 days for singleton pregnancies; p = 0.002). Bile acids reached significantly higher maximum blood levels in twin pregnancies (32.9 vs. 22.2 µmol/L; p = 0.012), and at a lower gestational age (gestational age maximum bile acids: 235 vs. 250 days; p < 0.001). No difference in pharmacological treatment was observed between the groups. Twin pregnancies with and without ICP had comparable pregnancy outcomes; however, ICP pregnancies had a higher incidence of gestational diabetes mellitus (15.7% vs. 5.2%; p = 0.03). In repeat pregnancies, ICP was diagnosed earlier in the twin pregnancy (p = 0.006). CONCLUSIONS: Compared to singleton pregnancies, twin pregnant women with ICP have an earlier diagnosis of ICP, and levels of bile acids are higher. Compared to twin pregnancies without ICP, the pregnancy outcomes are comparable.

Effect of gestational diabetes on fetal growth rate and later overweight in the offspring.

CONTEXT: Children of women with gestational diabetes (GDM) are often born with a higher birthweight and have an increased risk of overweight during childhood. High fetal growth rate is also associated with being overweight in childhood. OBJECTIVE: To examine excessive fetal growth rate as a mediator between GDM and overweight in the offspring. METHODS: This was a longitudinal cohort study, using routinely collected data on children born 2008-2014 in Aarhus, Denmark. Fetal biometrics were extracted from the patient records at Aarhus University Hospital and childhood weight from the health records at Aarhus Municipality Healthcare Service. We calculated growth trajectories for fetuses affected by GDM and for unaffected fetuses using cubic mixed model regression. We extracted individual fetal growth rate and estimated the contributing effect of fetal growth rate on the risk of being overweight in the 5-9 year-old offspring. RESULTS: We included 6794 mother-child pairs, 295 with GDM. Fetal growth was higher in women with GDM from week 25, and the offspring had an increased risk of being overweight (OR: 2.02 (95%CI: 1.44 - 2.84)). When adjusting for fetal growth rate in week 28 the effect attenuated by 15%, and to 1.10 (95%CI: 0.76 - 1.60) when further adjusting for pre-pregnancy BMI. CONCLUSION: Pregnancies affected by GDM had higher fetal growth rate and the offspring had a higher risk of being overweight at 5-9 years. Fetal growth rate in early third trimester was a mediator of up to 15% of this association, but pre-pregnancy BMI contributed strongly as well.

Hemoglobin A1c Trajectories During Pregnancy and Adverse Outcomes in Women With Type 2 Diabetes: A Danish National Population-Based Cohort Study.

OBJECTIVE: To identify and characterize groups of pregnant women with type 2 diabetes with distinct hemoglobin A1c (HbA1c) trajectories across gestation and to examine the association with adverse obstetric and perinatal outcomes. RESEARCH DESIGN AND METHODS: This was a retrospective Danish national cohort study including all singleton pregnancies in women with type 2 diabetes, giving birth to a liveborn infant, between 2004 and 2019. HbA1c trajectories were identified using latent class linear mixed-model analysis. Associations with adverse outcomes were examined with logistic regression models. RESULTS: A total of 1,129 pregnancies were included. Three HbA1c trajectory groups were identified and named according to the glycemic control in early pregnancy (good, 59%; moderate, 32%; and poor, 9%). According to the model, all groups attained an estimated HbA1c <6.5% (48 mmol/mol) during pregnancy, with no differences between groups in the 3rd trimester. Women with poor glycemic control in early pregnancy had lower odds of having an infant with large-for-gestational-age (LGA) birth weight (adjusted odds ratio [aOR] 0.57, 95% CI 0.40-0.83), and higher odds of having an infant with small-for-gestational age (SGA) birth weight (aOR 2.49, 95% CI 2.00-3.10) and congenital malformation (CM) (aOR 4.60 95% CI 3.39-6.26) compared with women with good glycemic control. There was no evidence of a difference in odds of preeclampsia, preterm birth, and caesarean section between groups. CONCLUSIONS: Women with poor glycemic control in early pregnancy have lower odds of having an infant with LGA birth weight, but higher odds of having an infant with SGA birth weight and CM.

Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes.

INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.

Clinical and Metabolic Characterization of Women With Gestational Diabetes Mellitus Within the First Year Postpartum.

Context: Women with gestational diabetes mellitus (GDM) have an increased risk of long-term complications, including impaired glucose metabolism, type 2 diabetes (T2DM), cardiovascular disease, and obesity. In current clinical practice, a 1 size fits all approach to GDM is applied, although heterogeneity among women with GDM has been recognized. Objective: To give the most adequate preventive care and postpartum (PP) guidance, we aimed to make a metabolic characterization and identify subgroups of women with previous GDM within the first year PP. Methods: In this prospective cohort study, we collected data in gestational week 34-38, at 3 months, and 1 year PP on women with GDM who participated in a PP follow-up program in Central Region Denmark from April 2019 to December 2022. Results: In total, 1270 women were included in the program in late pregnancy. Of the 768 women participating in either the oral glucose tolerance test 3 months PP (n = 545) or the 1-year follow-up (n = 493) or both (n = 261), 608 (79.2%) were normoglycemic, 137 (17.8%) had prediabetes, 20 (2.6%) had T2DM, and 3 (.4%) had developed T1DM. More than 40% of the women gained weight in the first year PP compared with their pregestational weight. Conclusion: Our study shows that 20.8% of women with GDM who volunteered to participate in a clinical follow-up program developed prediabetes or diabetes (T1DM and T2DM) within the first year PP. The GDM diagnosis encompasses a heterogenetic group of women and a deeper characterization may provide an opportunity for a more personalized risk assessment to prevent the progression to T2DM.

Advances in extracellular vesicles as mediators of cell-to-cell communication in pregnancy.

Cell-to-cell communication mediated by Extracellular Vesicles (EVs) is a novel and emerging area of research, especially during pregnancy, in which placenta derived EVs can facilitate the feto-maternal communication. EVs comprise a heterogeneous group of vesicle sub-populations with diverse physical and biochemical characteristics and originate by specific biogenesis mechanisms. EVs transfer molecular cargo (including proteins, nucleic acids, and lipids) between cells and are critical mediators of cell communication. There is growing interest among researchers to explore into the molecular cargo of EVs and their functions in a physiological and pathological context. For example, inflammatory mediators such as cytokines are shown to be released in EVs and EVs derived from immune cells play key roles in mediating the immune response as well as immunoregulatory pathways. Pregnancy complications such as gestational diabetes mellitus, preeclampsia, intrauterine growth restriction and preterm birth are associated with altered levels of circulating EVs, with differential EV cargo and bioactivity in target cells. This implicates the intriguing roles of EVs in reprogramming the maternal physiology during pregnancy. Moreover, the capacity of EVs to carry bioactive molecules makes them a promising tool for biomarker development and targeted therapies in pregnancy complications. This review summarizes the physiological and pathological roles played by EVs in pregnancy and pregnancy-related disorders and describes the potential of EVs to be translated into clinical applications in the diagnosis and treatment of pregnancy complications.

Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and ß-hydroxybutyrate in healthy young males.

BACKGROUND: The appetite-suppressing potential of liver-expressed antimicrobial peptide 2 (LEAP2), and its antagonistic effects on the hunger-inducing hormone ghrelin have attracted scientific interest. It is unclear how LEAP2 is influenced by fasting and how it responds to specific nutrients. OBJECTIVES: The purpose of this investigation was to assess whether LEAP2 concentration 1) decreases after fasting, 2) increases postprandially, and 3) is regulated by nutrient sensing in the splanchnic bed. METHODS: Plasma LEAP2 concentration was measured in blood samples from 5 clinical cross-over trials, following 1) 36 h of fasting (n = 8), 2) 10 h of fasting (n = 37, baseline data pooled from 4 of the clinical trials), 3) Oral and intravenous glucose administration (n = 11), 4) Oral and intravenous Na-lactate administration (n = 10), and 5) Oral and intravenous Na-ß-hydroxybutyrate (BHB) administration (n = 8). All 5 trials included healthy males. RESULTS: Compared with a 10-h fasting period, the median LEAP2 concentration was 38% lower following 36 h of fasting (P < 0.001). Oral administration of glucose elevated, whereas intravenous glucose administration lowered LEAP2 concentration (intervention x time, P = 0.001), resulting in a mean difference of 9 ng/mL (95% confidence interval [CI]: 1, 17) after 120 min. Oral lactate increased, and intravenous lactate decreased LEAP2 (intervention x time, P = 0.007), with a mean difference between interventions of 10 ng/mL (95% CI: 6, 15) after 120 min. In contrast, oral and intravenous administration of BHB reduced the LEAP2 concentration (main effect of time, P < 0.001). CONCLUSIONS: Our investigations show that LEAP2 concentration was lower after a 36-h fast than an overnight fast and that oral delivery of glucose and lactate elevated LEAP2 concentration compared with intravenous administration, whereas LEAP2 concentrations decreased with both oral and intravenous BHB. This indicates that the LEAP2 concentration is sensitive to intestinal exposure to specific substrates, highlighting the need for future studies exploring the relationship between nutrients and LEAP2. This trial was registered at clinicaltrials.gov as NCT01840098, NCT03204877, NCT04299815, NCT03935841, and NCT01705782.

Health promotion intervention among women with recent gestational diabetes mellitus: penetration, participation, and baseline findings from the Face-it randomized controlled trial.

INTRODUCTION: Face-it is a randomized controlled trial for women with recent gestational diabetes mellitus (GDM) and their families designed to evaluate the effect of a health promotion intervention on type 2 diabetes mellitus (T2DM) risk and quality of life. This study examined (1) the penetration and participation rates for the Face-it trial, (2) the characteristics of the participating women and the potential differences in characteristics according to partner participation status, and (3) representativity of the women at baseline. RESEARCH DESIGN AND METHODS: We identified women with GDM during pregnancy and invited them and their partners to a baseline examination 10-14 weeks after delivery. Representativity was assessed by comparing the baseline participants with non-participating women, the general population of women with GDM delivering in Denmark, and populations from other intervention trials. RESULTS: The penetration rate was 38.0% (867/2279) and the participation rate was 32.9% (285/867). The 285 women who attended baseline had a mean age of 32.7 (±4.8) years and body mass index (BMI) of 28.1 (±5.4) kg/m2, and 69.8% had a partner who participated. The women participating with a partner were more often primiparous, born in Denmark (82.8% vs 68.2%), were younger, and more often had a BMI ≤24.9 kg/m2 (35.7% vs 21.2%) compared with women without a partner. Compared with the general population of women with GDM in Denmark, these women broadly had similar degree of heterogeneity, but had higher rates of primiparity and singleton deliveries, and lower rates of preterm delivery and prepregnancy obesity. CONCLUSIONS: The penetration and participation rates were acceptable. We found a high rate of partner participation. Overall, women participating with a partner were comparable with those participating without a partner. Participating women were broadly similar to the general national GDM population, however with prepregnancy obesity, multiparity, preterm delivery, and multiple pregnancy being less represented. TRIAL REGISTRATION NUMBER: NCT03997773.

Whey Protein Premeal Lowers Postprandial Glucose Concentrations in Adults Compared with Water-The Effect of Timing, Dose, and Metabolic Status: a Systematic Review and Meta-analysis.

BACKGROUND: Serving whey protein before a meal in order to lower postprandial blood glucose concentrations is known as a premeal. The underlying mechanisms are only partly understood but may involve stimulation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin secretion together with a slower gastric emptying rate. OBJECTIVES: The objective of this systematic review and meta-analysis was to review all randomized clinical trials investigating premeals with whey protein in comparison with a nonactive comparator (control) that evaluated plasma glucose, GLP-1, GIP, insulin, and/or gastric emptying rate. Secondary aims included subgroup analyses on the timing and dose of the premeal together with the metabolic state of the participants [lean, obese, and type 2 diabetes mellitus (T2DM)]. METHODS: We searched EMBASE, CENTRAL, PUBMED, and clinicaltrials.gov and found 16 randomized crossover trials with a total of 244 individuals. The last search was performed on 9 August, 2022. RESULTS: Whey protein premeals lowered peak glucose concentration by -1.4 mmol/L [-1.9 mmol/L; -0.9 mmol/L], and the area under the curve for glucose was -0.9 standard deviation (SD) [-1.2 SD; -0.6 SD] compared with controls (high certainty). In association with these findings, whey protein premeals elevated GLP-1 (low certainty) and peak insulin (high certainty) concentrations and slowed gastric emptying rate (high certainty) compared with controls. Subgroup analyses showed a more pronounced and prolonged glucose-lowering effect in individuals with T2DM compared with participants without T2DM. The available evidence did not elucidate the role of GIP. The protein dose used varied between 4 and 55 g, and meta-regression analysis showed that the protein dose correlated with the glucose-lowering effects. CONCLUSIONS: In conclusion, whey protein premeals lower postprandial blood glucose, reduce gastric emptying rate, and increase peak insulin. In addition, whey protein premeals may elevate plasma concentrations of GLP-1. Whey protein premeals may possess clinical potential, but the long-term effects await future clinical trials.

Insulin Signaling Is Preserved in Skeletal Muscle During Early Diabetic Ketoacidosis.

BACKGROUND AND AIMS: During diabetic ketoacidosis (DKA), muscle tissue develops a profound insulin resistance that complicates reversal of this potentially lethal condition. We have investigated mediators of insulin action in human skeletal muscle during total insulin withdrawal in patients with type 1 diabetes, under the hypothesis that initial phases of DKA are associated with impaired postreceptor signaling. MATERIALS AND METHODS: Muscle biopsies were obtained during a randomized, controlled, crossover trial involving 9 patients with type 1 diabetes. The subjects were investigated during a high-dose insulin clamp preceded by either: (1) insulin-controlled euglycemia (control) or (2) total insulin withdrawal for 14 hours. Insulin action in skeletal muscle and whole-body substrate metabolism were investigated using western blot analysis and indirect calorimetry respectively. RESULTS: During insulin withdrawal, insulin-stimulated dephosphorylation of glycogen synthase decreased by ∼30% (P < .05) compared with the control situation. This was associated with a decrease in glucose oxidation by ∼30% (P < .05). Despite alterations in glucose metabolism, insulin transduction to glucose transport and protein synthesis (Akt, AS160, mammalian target of rapamycin, and eukaryotic translation initiation factor 4E binding protein) was intact, and glucose transporter (GLUT4) and mitochondrial proteins (succinate dehydrogenase complex, subunit A and prohibitin 1) protein expression were unaffected by the intervention. CONCLUSION: DKA impairs insulin-stimulated activation of glycogen synthase, whereas insulin signal transduction to glucose transport and protein synthesis remains intact. Reversal of insulin resistance during treatment of DKA should target postreceptor mediators of glucose uptake. CLINICAL TRIAL REGISTRATION NUMBER: NCT02077348.

Breastfeeding and insulin requirements in women with Type 1 diabetes mellitus in the first year postpartum.

AIMS: To explore whether breastfeeding affects postpartum insulin requirements, HbA1c levels, and pregnancy weight retention in women with Type 1 Diabetes Mellitus (T1DM). METHODS: This prospective study included 66 women with T1DM. The women were divided into two groups based on whether they were breastfeeding (BF) at 6 months postpartum (BFyes, n = 32) or not (BFno, n = 34). Mean daily insulin requirement (MDIR), HbA1c levels, and pregnancy weight retention at 5 time-points from discharge to 12 months postpartum were compared. RESULTS: MDIR increased by 35% from 35.7 IU at discharge to 48.1 IU at 12 months postpartum (p < 0.001). MDIR in BFyes and BFno were comparable, however in BFyes, MDIR were continuously lower compared to BFno. Postpartum HbA1c increased rapidly from 6.8% at 1 month to 7.4% at 3 months postpartum and settled at 7.5% at 12 months postpartum. The increase in HbA1c during the first 3 months postpartum was most pronounced in BFno (p < 0.001). Although neither were statistically significant, from 3 months postpartum HbA1c levels were highest in the BFno and BFno had a higher pregnancy weight retention compared to BFyes (p = 0.31). CONCLUSION: In women with T1DM, breastfeeding did not significantly affect postpartum insulin requirements, HbA1c levels or pregnancy weight retention in the first year after delivery.

Hyperglycemia in Pregnancy and Women's Health in the 21st Century.

Hyperglycemia is the commonest medical condition affecting pregnancy and its incidence is increasing globally in parallel with the twin epidemics of diabetes and obesity. Both pre-pregnancy diabetes and gestational diabetes are associated with short term pregnancy complications, with the risk of immediate complications generally broadly rising with more severe hyperglycemia. In this article we firstly consider these risks and their optimal management during pregnancy and then broaden our scope to consider the long-term implications of hyperglycemia in pregnancy as it relates to overall maternal and offspring health in a life course perspective.

[Pregnancy after simultaneouspancreasandkidney transplantation].

In this case report, a 41-year-old nullipara obtained pregnancy one and a half year after a simultaneous pancreas and kidney transplantation (SKP). After SKP, the woman had no need for insulin and no hypertension. Her kidney function was stable during pregnancy and no insulin was needed. During the last weeks of pregnancy, increased blood pressure was seen. Biochemically, there were no signs of preeclampsia and no proteinuria. An elective cesarean section was performed in gestational week 37+5 and a healthy boy, 2,710 g. (-1.2 standarddeviation) was born. Pregnancy after SKP is possible and can have a good prognosis.

Three months of melatonin treatment reduces insulin sensitivity in patients with type 2 diabetes-A randomized placebo-controlled crossover trial.

The use of the sleep-promoting hormone melatonin is rapidly increasing as an assumed safe sleep aid. During the last decade, accumulating observations suggest that melatonin affects glucose homeostasis, but the precise role remains to be defined. We investigated the metabolic effects of long-term melatonin treatment in patients with type 2 diabetes including determinations of insulin sensitivity and glucose-stimulated insulin secretion. We used a double-blinded, randomized, placebo-controlled, crossover design. Seventeen male participants with type 2 diabetes completed (1) 3 months of daily melatonin treatment (10 mg) 1 h before bedtime (M) and (2) 3 months of placebo treatment 1 h before bedtime (P). At the end of each treatment period, insulin secretion was assessed by an intravenous glucose tolerance test (0.3 g/kg) (IVGTT) and insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp (insulin infusion rate 1.5 mU/kg/min) (primary endpoints). Insulin sensitivity decreased after melatonin (3.6 [2.9-4.4] vs. 4.1 [3.2-5.2] mg/(kg × min), p = .016). During the IVGTT, the second-phase insulin response was increased after melatonin (p = .03). In conclusion, melatonin treatment of male patients with type 2 diabetes for 3 months decreased insulin sensitivity by 12%. Clinical use of melatonin treatment in dosages of 10 mg should be reserved for conditions where the benefits will outweigh the potential negative impact on insulin sensitivity.

The Arg82Cys Polymorphism of the Protein Nepmucin Implies a Role in HDL Metabolism.

Context: Blood lipid levels are linked to the risk of cardiovascular disease and regulated by genetic factors. A low-frequency polymorphism Arg82Cys (rs72836561) in the membrane protein nepmucin, encoded by CD300LG, is associated with lower fasting concentration of high-density lipoprotein cholesterol (HDLc) and higher fasting triglycerides. However, whether the variant is linked to postprandial lipids and glycemic status remains elusive. Objective: Here, we augment the genetic effect of Arg82Cys on fasting plasma concentrations of HDL subclasses, postprandial lipemia after a standardized high-fat meal, and glycemic status to further untangle its role in HDL metabolism. Methods: We elucidated fasting associations with HDL subclasses in a population-based cohort study (Oxford BioBank, OBB), including 4522 healthy men and women. We investigated fasting and postprandial consequences on HDL metabolism in recall-by-genotype (RbG) studies (fasting: 20 carrier/20 noncarrier; postprandial: 7 carrier/17 noncarrier), and shed light on the synergistic interaction with glycemic status. Results: A lower fasting plasma concentration of cholesterol in large HDL particles was found in healthy male carriers of the Cys82 polymorphism compared to noncarriers, both in the OBB (P = .004) and RbG studies (P = .005). In addition, the Cys82 polymorphism was associated with low fasting plasma concentrations of ApoA1 (P = .008) in the OBB cohort. On the contrary, we did not find differences in postprandial lipemia or 2-hour plasma glucose levels. Conclusion: Taken together, our results indicate an association between the Arg82Cys variant and a lower concentration of HDL particles and HDLc, especially in larger HDL subclasses, suggesting a link between nepmucin and HDLc metabolism or maturation.